ABSTRACT
Avian A/H5N1 influenza viruses pose a pandemic threat. As few as five amino acid substitutions, or four with reassortment, might be sufficient for mammal-to-mammal transmission through respiratory droplets. From surveillance data, we found that two of these substitutions are common in A/H5N1 viruses, and thus, some viruses might require only three additional substitutions to become transmissible via respiratory droplets between mammals. We used a mathematical model of within-host virus evolution to study factors that could increase and decrease the probability of the remaining substitutions evolving after the virus has infected a mammalian host. These factors, combined with the presence of some of these substitutions in circulating strains, make a virus evolving in nature a potentially serious threat. These results highlight critical areas in which more data are needed for assessing, and potentially averting, this threat.
Subject(s)
Evolution, Molecular , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Influenza A Virus, H5N1 Subtype/genetics , Influenza A Virus, H5N1 Subtype/pathogenicity , Influenza, Human/virology , Orthomyxoviridae Infections/virology , RNA-Dependent RNA Polymerase/genetics , Respiratory System/virology , Viral Proteins/genetics , Adaptation, Physiological , Air Microbiology , Amino Acid Substitution , Animals , Birds , Genetic Fitness , Glycosylation , Hemagglutinin Glycoproteins, Influenza Virus/metabolism , High-Throughput Nucleotide Sequencing , Humans , Influenza in Birds/virology , Influenza, Human/immunology , Influenza, Human/transmission , Mammals , Models, Biological , Mutation , Orthomyxoviridae Infections/transmission , Probability , Receptors, Virus/metabolism , Selection, Genetic , Sialic Acids/metabolismABSTRACT
Antigenic and genetic analysis of the hemagglutinin of approximately 13,000 human influenza A (H3N2) viruses from six continents during 2002-2007 revealed that there was continuous circulation in east and Southeast Asia (E-SE Asia) via a region-wide network of temporally overlapping epidemics and that epidemics in the temperate regions were seeded from this network each year. Seed strains generally first reached Oceania, North America, and Europe, and later South America. This evidence suggests that once A (H3N2) viruses leave E-SE Asia, they are unlikely to contribute to long-term viral evolution. If the trends observed during this period are an accurate representation of overall patterns of spread, then the antigenic characteristics of A (H3N2) viruses outside E-SE Asia may be forecast each year based on surveillance within E-SE Asia, with consequent improvements to vaccine strain selection.
Subject(s)
Disease Outbreaks , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Influenza A Virus, H3N2 Subtype , Influenza, Human/epidemiology , Antigenic Variation , Asia/epidemiology , Asia, Southeastern/epidemiology , Europe/epidemiology , Evolution, Molecular , Forecasting , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Humans , Influenza A Virus, H3N2 Subtype/classification , Influenza A Virus, H3N2 Subtype/genetics , Influenza A Virus, H3N2 Subtype/immunology , Influenza A Virus, H3N2 Subtype/isolation & purification , Influenza Vaccines , Influenza, Human/virology , North America/epidemiology , Oceania , Phylogeny , Population Surveillance , Seasons , South America/epidemiologyABSTRACT
Annual influenza epidemics in humans affect 5-15% of the population, causing an estimated half million deaths worldwide per year [Stohr K. Influenza-WHO cares. Lancet Infectious Diseases 2002;2(9):517]. The virus can infect this proportion of people year after year because the virus has an extensive capacity to evolve and thus evade the immune response. For example, since the influenza A(H3N2) subtype entered the human population in 1968 the A(H3N2) component of the influenza vaccine has had to be updated almost 30 times to track the evolution of the viruses and remain effective. The World Health Organization Global Influenza Surveillance Network (WHO GISN) tracks and analyzes the evolution and epidemiology of influenza viruses for the primary purpose of vaccine strain selection and to improve the strain selection process through studies aimed at better understanding virus evolution and epidemiology. Here we give an overview of the strain selection process and outline recent investigations into the global migration of seasonal influenza viruses.
